Comment. The anti-aggression actions of GHK, if scaled up for a human, would occur at a dosage of about 0.3 mgs. The GHK is produced in Russia at the State University of Saint Petersburg, Putin's school. So the Russians can spray opposing armies with GHK and turn them into 1970s style California flower children.

Effects of Tripeptide Gly-His-Lys in Pain-Induced Aggressive-Defensive Behavior in Rats

We studied the effect of Gly-His-Lys tripeptide administered intraperitoneally in doses of 5, 15, 50 and 150 μg/kg on pain-induced aggressive-defensive behavior. A foot-shock model of aggression in rats grouped in pairs in an electrified chamber was used. Analgesic and antiaggresiogenic effects of the peptide were demonstrated. It was found the L-lysine residue plays the key role in these effects, because they were observed under the influence of L-lysine administration in doses close to its equimolar content in the studied tripeptide.

Anti-anxiety actions

Comment. There are two studies on the anti-anxiety actions of GHK, a maze test and a open grassy field test. The dosage of GHK inducing the anti-anxiety effects is very low and would correspond to about 35 micrograms in humans. There are 3 times more complaints to physicians about anxiety than there are for depression.

Intraperitoneal administration of tripeptide Gly-His-Lys to male rats in doses of 0.5, 5, and 50 μg/kg 12 min before the start of the experiment produced an anxiolytic effect in the elevated plus maze test manifested in an increase in the time spent in open arms and shortened time spent in the closed arms. The anxiolytic effect was most pronounced after injection of 0.5 μg/kg peptide and decreased with increasing the dose of the peptide. Replacement of L-lysine with D-lysine in the tripeptide molecule was accompanied by a significant weakening of the neurotropic effects in all studied doses. Attachment of D-alanine to N- or C-terminus of Gly-His-Lys peptide leveled its anxiolytic action in all doses; significant changes in some measures of increased anxiety after administration at 50 μg/kg were found.

The tripeptide Gly-His-Lys (hepatocyte growth factor) administered intraperitoneally 12 minutes before the experiment in single doses of 0.5, 5 and 50 mg /kg in the test “open field” with exposure time of 5 minutes in all the doses caused a reduction of fear and anxiety manifested themselves in increasing the exploratory activity and decreasing the immobility reaction both in the peripheral and in the central parts of the “open field”. Emotionality indices (grooming and defecation) did not change significantly. The character of the obtained results suggests the presence of the peptide neurotropic effects, including anxiolytic one.

Anti-pain

Comment. We often receive comments from persons with chronic severe pain that requires use of strong opioids such as fentanyl. They are using GHK-Cu for skin effects and notice a sharp reduction in pain in another area of their body. Then they are able to reduce their opioid use. The effective dosage used in the mice, if scaled up for humans would be about 35 mgs.

Effect of Gly-His-Lys peptide and its analogs on pain sensitivity in mice

The intraperitoneal administration of Gly-His-Lys tripeptide to male BALB/c mice 12 min before the beginning of the study at doses 0.5, 1.5, 5, 15, and 50 mg/kg produced analgesic effect in the hot-plate test, which was manifested by an increase in the duration of the latent period of the paw-licking reaction. The replacement of L-lysine by D-lysine in the tripeptide molecule was accompanied by significant weakening of the analgesic effect after administration in the same doses. The attachment of D-alanine to N- or C-end of Gly-His-Lys peptide led to leveling of the analgesic effect. On the contrary, after the administration of these analogs, the duration of the latent period of the paw-licking reaction was increased in almost all experimental groups of animals and reached in some cases significant differences that were indicative of the manifestation of algic effects of the modified peptides.

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